SOX2 and Bcl-2 as a Novel Prognostic Value in Hepatocellular Carcinoma Progression

Sex-determining region Y-box 2 (SOX2) is a stem cell transcription factor and a major regulator of self-renewal and pluripotency of cancer stem cells (CSCs). In many types of cancer, SOX2 is dysregulated due to overexpression associated with tumor progression and low survival rate. Many HCC cases encounter recurrence and metastasis which might be due to CSCs and also apoptosis. Since little is known about the expression pattern of SOX2 and apoptotic genes in HCC, we aimed to determine the prognostic significance of SOX2, Bax, and Bcl-2 in clinicopathological features, tumor progression, and survival rate of the HCC patients. The expression of SOX2, Bax, and Bcl-2 were evaluated using qRT-PCR in 53 formalin-fixed, paraffin-embedded tissues (FFPE) of patients and 44 controls. Correlation of these genes was analyzed with clinicopathological features and tumor progression. The correlationship between SOX2 expression and ALBI grade as prognostic indicators were calculated. Survival rates were determined by Kaplan–Meier survival curves. SOX2 and Bcl-2 were remarkably overexpressed in HCC patients compared to controls (p = 0.04 and p = 0.003, respectively). A significant association was found for both SOX2 and Bcl-2 overexpression with TNM staging (p = 0.02, p = 0.04) and tumor grading (p = 0.01, p = 0.003), respectively. A significant correlation was observed: patients with SOX2 overexpression had a lower 5-year overall survival rate (p = 0.04); however, there was no significant association between Bcl-2 and survival (p = 0.5). Collectively, overexpression of SOX2 and Bcl-2, alone or combined, may be a potential marker to evaluate prognosis and response to HCC treatment

Enhancement of immune responses by vaccine potential of three antigens, including ROP18, MIC4, and SAG1 against acute toxoplasmosis in mice

Toxoplasma gondii (T. gondii) causes considerable financial losses in the livestock industry and can present serious threats to pregnant women, as well as immunocompromised patients. Therefore, it is required to design and produce an efficient vaccine for controlling toxoplasmosis. The present study aimed to evaluate the protective immunity induced by RMS protein (ROP18, MIC4, and SAG1) with Freund adjuvant, calcium phosphate nanoparticles (CaPNs), and chitosan nanoparticles (CNs) in BALB/c mice. The RMS protein was expressed in Escherichia coli (E. coli) and purified using a HisTrap HP column. Thereafter, cellular and humoral immunity was assessed by injecting RMS protein on days 0, 21, and 35 into four groups [RMS, RMS-chitosan nanoparticles (RMS-CNs), RMS-calcium phosphate nanoparticles (RMS-CaPNs), and RMS-Freund]. Phosphate buffered saline (PBS), CNs, CaPNs, and Freund served as the four control groups. The results displayed that vaccination with RMS protein and adjuvants significantly elicited the levels of specific IgG antibodies and cytokines against toxoplasmosis. There were high levels of total IgG, IgG2a, and IFN-γ in vaccinated mice, compared to those in the control groups, especially in the RMS-Freund, indicating a Th-1 type response. The vaccinated and control mice were challenged intraperitoneally with 1 × 103 tachyzoites of the T. gondii RH strain four weeks after the last injection, and in RMS-Freund and RMS-CaPNs groups, the highest increase in survival time was observed (15 days). The RMS can significantly increase Th1 and Th2 responses; moreover, multi-epitope vaccines with adjuvants can be a promising strategy for the production of a vaccine against toxoplasmosis

Th1 and Th2 Immune response in Hymenolepis nana infection

Background & Objective: Although many experimental studies provide convincing evidence, that type II immunity is protective against helminthes, recent data in mice reveal that Th1 are also important in some cestods like Hymenolepis nana. To reveal the role of Th1 and Th2 lymphocyte in immunity against H.nana, the levele of IL12, IFNγ, IL5, IL13 was determined in serum of human infected with H.nana. Materials & Methods: In a case control study in 2006 in Mazandaran Medical Sciences university a total of 31 patients (case) with H.nana infection and 30 clinical healthy people (control) were included in this study. Measurment of IL12, IFNγ, IL13 and IL5 in serum samples were performed by solid-phase sandwich enzyme linked immunosorbant assay. Differential leukocyte count also was done. T test, mannwhitney test and wilcoxan W test were used for data analysis. Results: The mean concentration of IFNγ, IL13, IL12, IL5 in the sera of patient with H.nana infection were higher than control group, but only the difference between concentration of IFNγ (P<0.05) and IL13 (P<0.05) in two groups were significant. There was an increase in percentage of monocytes, Eosinophils and lymphocytes in patient when compared to the control group, but this increase was not significant. Conclusion: Results form the present study are in agreement with experimental study in that both Th1 and Th2 responses occurs in H.nana infection

Relationship between Maternal Serum Androgen Levels and Success Rate in ICSI Procedure

Background and purpose: Androgens play a key role in growth of ovarian follicles and female fertility in the process of in vitro fertilization. This study was performed to determine the relationship between androgen levels and success rate in Intracytoplasmic sperm injection (ICSI). Materials and methods: A nested case-control study was carried out in 60 infertile women attending the Infertility Treatment Center in Sari Imam Khomeini Hospital. They underwent agonist protocol and their levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and dehydro epiandrosterone-sulfate (DHEA-S) were measured on days three of menstrual cycle and ICSI cycle, day six of gonadotropin injection, and the day of human chorionic gonadotropin (HCG) injection. Data were analyzed in SPSS V18 applying independent T-test. Results: The mean age of participants was 30.1± 6.1 years. Among the subjects, 16 (26.7%) became pregnant and 44 (73.3%) did not become pregnant. On day three of ICSI cycle and before the onset of HCG injection, testosterone level was 0.88 ± 0.68 ng/ml in pregnant women and 0.53 ± 0.25 ng/ml in non-pregnant women (P= 0.012). The levels of DHEA-S were 2.79 ± 1.87 µg/l and 1.62 ± 1.45 µg/l in pregnant and non-pregnant women, respectively (P= 0.02). Conclusion: Androgen levels can play a significant role in the success of ICSI cycle, so, androgen therapy can be an attractive hypothesis for improving ovarian response and used as a treatment option to increase the success of in vitro fertilization

Blood groups: In Health and Diseases

ABO blood type antigens are polymorphic, inherited structures presented on the surface of red blood cells. Although ABO blood group antigens is the most important antigens in transfusion medicine, its main role is not clearly clarified. Correlation between ABO blood group and susceptibility to certain infectious and non-infectious diseases is a controversial issue. Since, lack of blood type antigens has not been related to significant diseases or health risks. There are many research studies that suffice to prove that blood antigens are biologically active, carbohydrate structures involving to the &ldquo;cell physiology and human pathology&rdquo;. This review summarizes the available data concerning the blood group antigens correlation with different aspects of health. We therefore investigated that certain blood type antigens can affect susceptibility to diseases or make a phenotype resistant

Inflammation, a Key Factor in Cancer Ambush

Inflammatory condition is the consequence of defensive mechanism of immune system against viral and bacterial infection, tissue injury, UV radiation, stress and etc. Persistently acute inflammation leads to chronic phase which is characterized by production of pro-inflammatory mediators from T cells. These molecules (e.g. IL-6, TNF-&alpha, IL-1&beta and IL-17) are mostly pleiotropic cytokines involved in multiple signaling cascades. NF-&kappaB, STAT3, and HIF-1&alpha are the major engaged pathways directing to several downstream targets associating with tumorigenesis and inflammation. Carcinogenesis processes such as DNA mutation/damage, proliferation, angiogenesis, apoptosis, and invasion are implicated to inflammation. Clearly there is a closely association between cancer and inflammation reported as “Seven Hallmark of Cancer”. The elucidation of relationship between inflammation and cancer and their interaction may result in effective therapy and prevention. Gastric cancer is one of the main cancer involved in complex correlation of inflammation and cancer. Inflammation in gastric epithelium could trigger cellular transformation and promote invasion by inducing immune responses and utilizing signaling cascades. Gastric tumor microenvironment has inverse association by providing cytokines and inflammatory mediators. This closely relationship facilitates gastric tumor development and the induction of chronic inflammation in tumor microenvironment. The current review will focus on describing the possible and critical ways in which inflammation and cancer are linked together with specific view to gastric cancer and inflammation. Finally, it introduces some putative treatment generally used in this way in order to direct more attention for further exploration

Evaluation on antibiotic resistance of helicobacter pylori isolated from patients admitted to tooba medical center, Sari

(Received 17 March, 2009; Accepted 8 July, 2009)AbstractBackground and purpose: Helicobacter pylori, which infect approximately one half of the world’s population, are an important risk factor in chronic gastritis, peptic ulcer disease, and gastric cancer. H. pylori eradication is now widely recommended as the most effective treatment of peptic ulcer disease. One of the most important reasons for treatment failure is H. pylori resistance to the antimicrobials usage in therapy. The aim of this study was to determine susceptibility patterns of H. pylori isolates in 6 routine anti-microbial agents in Northern Iran.Materials and methods: 125 patients from Tooba Medical Center in Sari with endoscopic evidence of dyspepsia complaints were used for obtaining gastric biopsies specimens. Biopsies were sent to the laboratory in thioglycolate broth (transport medium). Bacteria were primarily cultured on Columbia agar supplemented with 7% horse blood, 7% fetal calf serum. Urease, Catalase and Oxidase activities were used for H. pylori identification. Bacterial suspensions equivalent to 3 Mc. Farlands were spread on plates, along with antibiotic disks and placed in the diameter zone. Inhibition was measured after 3 days of incubation in micro-aerophilic condition.Results: H. pylori were isolated from 116(92.8%) subjects, a total of 125 biopsy specimens. Resistance to metronidazole, amoxicillin, clarithromycin, tetracycline, furazolidone and ciprofloxacin were 71%, 35%, 25%, 9%, 24% and 25%, respectively. Multiple resistance (amoxicillin-clarithromycin-metronidazole) were found in (6)5% of the isolates.Conclusion: Comparison of our data with previous results showed that prevalence of H. pylori resistance to clarithromycin, furazolidone and metronidazole has increased in Iran considerably. Resistance to amoxicillin in our study was too high in comparison with foreign studies. The present study demonstrates the need for continuous monitoring of the antimicrobial susceptibility in H. pylori in order to determine the optimal drug regimens.J Mazand Univ Med Sci 2009; 19(70): 26-32 (Persian

Serum TNF-α, IL-10 and IL-2 in Schizophrenic Patients Before and After Treatment with Risperidone and Clozapine

ABSTRACT Background: Schizophrenia is a disorder of the executive function of both sensory and central nervous system. Recent studies suggest that immune mechanisms play a role in the pathophysiology of this disease. The variations in cytokine concentrations have been associated with psychopathology and treatment of schizophrenia. Objective: To investigate the changes in serum concentrations of TNF-α, IL-10, and IL-2 in schizophrenic patients before and 40 days after treatment. Methods: In a case-control study, 26 schizophrenic patients and 26 healthy individuals were enrolled as the control group. PANSS scale questionnaire was used for diagnosis and assessing the severity of the disease. All patients were then treated with risperidone or clozapine for 40 days. Serum concentrations of TNF-α, IL-10 and IL-2 were measured by ELISA before and after treatment in both groups. Paired t-test and Independent t-test were used for comparison of data. Results: Comparison of TNF-α and IL-10 concentrations in patients before and after treatment revealed a significance decrease of TNF-α and increase of IL-10 concentrations (p=0.002, and p=0.008, respectively). Serum concentrations of IL-2 were lower than the detection limit of assay and were not detectable. In comparison with healthy controls, serum concentrations of TNF-α in schizophrenic patients were higher, while IL-10 concentrations were lower before treatment although the differences were not significant (p=0.291 and p=0.375, respectively). There was no correlation between cytokine concentrations and the positive and negative scale (PANSS). Also no significant difference in the admission, relapses, and duration of illness before and after treatment was observed. Conclusions: Increase of TNF-α and decrease of IL-10 may have an important role inpsychopathology of schizophrenia

Generation of CHO Stable Cell Line Overexpressing HER2: an In Vitro Model for Breast Cancer

Background: Breast cancer is the most common female malignancy and the leading cause of cancer mortality in women worldwide. The human epidermal growth factor receptor2 (HER2) is a transmembrane tyrosine kinase receptor that is usually overexpressed in human breast cancers. Stable cell lines heterogeneously overexpressing HER2 are highly required as in vitro models for breast cancer research. The aim of this study was to establish a stable cell line overexpressing HER2. Materials and Methods: CHO Cells were transfected with linearized pCVN/HER2 plasmid and selected for the recombinant cells with G418 antibiotic. Expression of HER2 in the transfected cells was analyzed using western blotting and immunofluorescence. Results: We found that the recombinant cells stably expressed high levels of HER2 proteins that were mostly concentrated on the cell membrane. Conclusions: The cell line established here provides a useful in vitro model for breast cancer research and any HER-related studies